This invention relates to x-ray contrast agents and, more particularly, to novel nonionic x-ray contrast agents, radiological compositions containing such agents and methods for X-ray visualization utilizing such compositions.
Nonionic contrast agents for intravascular and central nervous system visualization are complex molecules. As is known, the iodine in the molecule provides opacification to the x-rays. The remainder of the molecule provides the framework for transport of the iodine atoms. However, the structural arrangement of the molecule is important in providing stability, solubility and biological safety in various organs. A stable carbon-iodine bond is achieved in most compounds by attaching it to an aromatic nucleus. An enhanced degree of solubility as well as safety is conferred on the molecule by the addition of suitable solubilizing and detoxifying groups.
Furthermore, several features are desirable for intravascular and central nervous system nonionic agents. These include (1) maximum opacity to x-ray , (2) biological safety, (3) high water solubility, (4) chemical stability, (5) low osmolality, (6) no ionic charge, and (7) low viscosity.
There is a continuing need for nonionic contrast agents which meet all or substantially all the foregoing criteria. In addition to preparing the stable, water-soluble and safe agents, the recent studies have been in the development of low osmolality agents. Studies have shown that high osmolality can be correlated with many of the undesirable physiologic adverse reactions after the x-ray contrast medium intravenous injection, e.g. nausea, vomiting, heat and pain. The most recent major improvement is the introduction of low osmolar, nonionic agents, such as iopamidol, iohexol and ioversol. These new low osmolar agents provide patient comfort by causing less nausea and vomiting on intravenous injection and much less pain on peripheral arterial injection.